Brief Article
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World J Gastroenterol. Feb 28, 2011; 17(8): 1036-1044
Published online Feb 28, 2011. doi: 10.3748/wjg.v17.i8.1036
miR-200 family expression is downregulated upon neoplastic progression of Barrett’s esophagus
Cameron M Smith, David I Watson, Mary P Leong, George C Mayne, Michael Z Michael, Bas PL Wijnhoven, Damian J Hussey
Cameron M Smith, David I Watson, Mary P Leong, George C Mayne, Damian J Hussey, Department of Surgery, Flinders University, Bedford Park, South Australia 5042, Australia
Michael Z Michael, Department of Gastroenterology and Hepatology, Flinders University, Bedford Park, South Australia 5042, Australia
Bas PL Wijnhoven, Department of Surgery, Erasmus Medical Centre, PO Box 2040, 3000 CA, Rotterdam, The Netherlands
Author contributions: Hussey DJ and Smith CM conceived the experiments and analyzed the data; Smith CM, Leong MP and Mayne GC carried out the experiments; Watson DI, Wijnhoven BPL and Michael MZ contributed to study design and analyzed the data; all authors were involved in writing the paper and had final approval of the submitted version.
Supported by National Health and Medical Research Council, Australia
Correspondence to: Dr. Damian J Hussey, Department of Surgery, Flinders University, Flinders Medical Centre, Room 3D213, Bedford Park, South Australia 5042, Australia. damian.hussey@flinders.edu.au
Telephone: +8-618-82046091 Fax: +8-618-82046130
Received: July 21, 2010
Revised: September 13, 2010
Accepted: September 20, 2010
Published online: February 28, 2011
Abstract

AIM: To investigate miR-200 family expression in Barrett’s epithelium, gastric and duodenal epithelia, and esophageal adenocarcinoma.

METHODS: Real-time reverse transcriptase-polymerase chain reaction was used to measure miR-200, ZEB1 and ZEB2 expression. Ingenuity Pathway Analysis of miR-200 targets was used to predict biological outcomes.

RESULTS: Barrett’s epithelium expressed lower levels of miR-141 and miR-200c than did gastric and duodenal epithelia (P < 0.001). In silico analysis indicated roles for the miR-200 family in molecular pathways that distinguish Barrett’s epithelium from gastric and duodenal epithelia, and which control apoptosis and proliferation. All miR-200 members were downregulated in adenocarcinoma (P < 0.02), and miR-200c expression was also downregulated in non-invasive epithelium adjacent to adenocarcinoma (P < 0.02). The expression of all miR-200 members was lower in Barrett’s epithelium derived high-grade dysplastic cell lines than in a cell line derived from benign Barrett’s epithelium. We observed significant inverse correlations between miR-200 family expression and ZEB1 and ZEB2 expression in Barrett’s epithelium and esophageal adenocarcinoma (P < 0.05).

CONCLUSION: miR-200 expression might contribute to the anti-apoptotic and proliferative phenotype of Barrett’s epithelium and regulate key neoplastic processes in this epithelium.

Keywords: miRNA; Barrett’s esophagus; Esophageal adenocarcinoma; miR-200; Epithelial to mesenchymal transition; Apoptosis; Proliferation; Epithelium